Pentamidine is a synthetic diamidine that is used to prevent or treat African sleeping sickness and to treat pneumocystis pneumonia. Because of the latter indication and the advent of Acquired Immune Deficiency Syndrome (AIDS), use of pentamidine in the United States has risen sharply. We recently developed a sensitive bioassay for pentamidine. We are seeking support in order to continue studies of the distribution and elimination of the drug in experimental animals and humans. A better understanding of the pharmacokinetics of pentamidine may assist in the design of more effective and less toxic therapeutic or prophylactic regimens. We propose to determine the peak concentrations and rates of disappearance of pentamidine from serum of humans who receive it by intramuscular injection or intravenous infusion. Concentrations of pentamidine will be determined in extracts of organs obtained at autopsy. Studies are also proposed to determine tissue concentrations in rats after single or multiple intravenous or intramuscular injections, serum concentrations in rabbits given a single intramuscular dose or the same dose by rapid intravenous injection, and serum and tissue concentrations in rats treated by gavage or by exposure to aerosolized drug. The principle objective is to determine how the route of administration affects the magnitude and persistence of pentamidine in serum and tissue. The assay we developed provides a new tool. Support will permit application of this tool to the study of fundamental pharmacokinetic characteristics of pentamidine.